Clinical breast examination (CBE) is one of the most common breast cancer screening modalities, but factors that affect its sensitivity are not well understood. We examined the association between CBE sensitivity and tumor, breast and personal characteristics among members of a managed care organization's Breast Cancer Screening Program (BCSP). The study population was 468 screened women 40 years and older diagnosed with invasive breast cancer between 1988 and 1994 within 1 year of a screening CBE. Logistic regression was used to evaluate the likelihood of a true positive versus a false negative CBE result, after adjustment for age, body weight and tumor size. CBE sensitivity increased with larger tumor size (17% for tumors < or = 0.5 cm and 58% for tumors > or = 2.1 cm, adjusted p for trend < 0.001) and decreased with higher body weight (48 and 23% for the lowest and highest quartiles, adjusted p for trend < 0.001). CBE was more sensitive in Asian women compared to white women (88% v.s. 35%, adjusted p = 0.04) and in current users of estrogen and progesterone combination therapy compared to never/former users (52% v.s. 33%, adjusted p = 0.08). There was an inverted U-shaped association between age and CBE sensitivity (40-49: 26%, 50-59: 48%, 60-69: 36%, 70-79: 33%, 80+: 18%, significant for oldest and youngest groups v.s. age 50-59 years). These findings suggest certain groups of women, for example, obese women and younger women, receive less benefit from CBE.