Data from a multicentric case-control study on breast cancer conducted in Italy were used to analyze the relationship of occupational and leisure-time physical activity with breast cancer risk. Cases were 2569 histologically confirmed incident breast cancer cases, and controls were 2588 patients admitted to the same network of hospitals of cases for acute, nonneoplastic, nonhormone related diseases. After allowance for major identified potential confounding factors (including an estimate of total calorie intake), the odds ratios (ORs) were 0.70, 0.71, 0.64, and 0.54 in subsequent levels of physical activity at work at ages 30-39, compared to the lowest level. The association was similar for occupational physical activity at ages 15-19 and still apparent at ages 50-59, with risk estimates of 0.86, 0.85, 0.85, and 0.62. The ORs for the highest versus the lowest category of leisure-time physical activity were also below unity (ORs for the highest level of leisure-time physical activity at ages 15-19, 0.95; at ages 30-39, 0.76; and at ages 50-59, 0.66). The protection of physical activity was apparently stronger below age 60 at diagnosis and was consistent across the strata of selected covariates, although the protection was somewhat greater for more educated women.