Background: Pathology diagnoses in a well-characterized population of women can be used to identify tissue sampling and diagnosis trends following mammography. Methods: Screening and diagnostic mammography, patient characteristics, and pathology reports from the BCSC performed from 1996-2008 were identified. Diagnosis was based on the most severe pathology interpretation in the same breast within 60 days of a post-mammogram tissue sample. Age, mammogram year and type, breast density, and family history of breast cancer were evaluated for associations with tissue sampling and most severe pathology diagnosis. Results: 4,022,506 mammograms (88.5% screening; 11.5% diagnostic) were performed in 1,288,886 women; 76,567 (1.9%) were followed by tissue sampling (1.2% screening; 7.1% diagnostic). Tissue sampling frequency following diagnostic mammography increased over time in women over 50 but remained stable following screening mammography. The frequency of invasive cancer increased with age and was more common following a diagnostic (29.3%) vs screening (19.8%) mammogram; the frequency of high risk lesions (ADH; lobular neoplasia) was highest in women aged 50-59. For tissue sampling following screening mammograms, the frequency of DCIS increased over time while benign diagnoses decreased. No significant time trends were noted for diagnoses associated with diagnostic mammograms. Women aged 40-59 with dense breasts and a tissue sampling following screening mammogram had a significantly higher frequency of DCIS (40-49: 4.8% vs 3.2%, P< 0.001; 50-59: 7.0% vs 5.7%, P=0.007). Women aged 40-59 with > 1first degree relative with breast cancer vs none that had a tissue sampling following screening mammogram had a significantly higher frequency of invasive cancer (40-49: 11.4% vs 9.4%, p=0.008; 50-59: 19.8% vs 18.2%, p =0.086) and DCIS (40-49: 6.2% vs 4.0%, p< 0.001; 50-59: 8.2% vs 6.2%, p< 0.001). Conclusions: There was an increase in DCIS and a decrease in benign diagnoses in tissues samples after screening mammography over time. No trends were seen following diagnostic mammography. DCIS was also more frequent in women with dense breasts.