BACKGROUND: While screening has been demonstrated to reduce breast cancer mortality, the optimal screening interval is unknown. We designed a study to determine the risk of an advanced breast cancer diagnosis by varying the interval between mammograms. METHODS: We reviewed a single state's mammography records of women diagnosed with breast cancer between 1994 and 2002. The pre-diagnosis screening interval was the number of days between the last two eligible mammograms preceding a cancer diagnosis. The interval was classified as annual (0.75-1.49 years), biennial (1.5-2.49 years) or longer (exceeding 2.49 years). Advanced breast cancer was>or=stage IIB, tumor size>2 cm, or>or=one lymph node with cancer. RESULTS: The probability of an advanced breast cancer diagnosis did not differ between women with an annual pre-diagnosis screening interval and women with a biennial interval (21.1% vs. 23.7%, P=0.262). A longer pre-diagnosis screening interval was weakly associated with advanced breast cancer (21.8% for intervals 0.75-2.49 years vs. 26.8% for longer intervals, P=0.070). In multivariate analysis, we found an interaction between the pre-diagnosis screening interval and age. Among women 50 years or older, the risk of an advanced breast cancer diagnosis risk was higher for women with a pre-diagnosis screening interval exceeding 2.49 years compared to women with shorter screening intervals (OR 1.99 [1.02-3.90]). CONCLUSIONS: We found no difference in advanced breast cancer rates between women using mammography annually or biennially. Among women 50 years or older, the advanced breast cancer rate increased when the pre-diagnosis screening interval exceeded 2.49 years.