Background: Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. Objectives: To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. Methods: A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost–utility of differing surveillance regimens. Results: The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring > 20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was < 10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. Limitations: Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. Conclusions: Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. Funding: The National Institute for Health Research Health Technology Assessment programme.