Renal cell carcinoma (RCC) is more common in men than women although the relationship between sex and histologic sub-type of RCC is unknown. The Columbia University Urologic Oncology Database of 1,105 patients who underwent nephrectomy from 1990-2005 was reviewed. 1,018 patients were included who underwent renal surgery with complete demographic data and post-operative pathologic information; 49 with incomplete information and 36 with "granular" histology were excluded. Differences in histology, size and volume of primary tumor, laterality, chief complaint, age, pathologic stage and status were evaluated by sex using ANOVA techniques. The cohort included 671 (66.1%) men and 344 (33.8%) women. There were no differences in age (61.0 vs. 60.7 years, P = 0.36), size (6.22 vs. 5.53 cm, P = 0.08) or volume (305 vs. 129cc, P = 0.07) of primary tumor. Men were more likely to have bilateral tumors (9.6 vs. 3.5%, P = 0.003). A greater percentage of men had malignant pathologic histology at nephrectomy (90.9 vs. 84.0%, P = 0.002). The rate of malignancy for women increased from 44.5% for tumors < 1 cm to 92.7% for tumors greater than 10 cm; there was no trend noted in men. Women had a greater percentage of conventional RCC (77.2 vs. 70.5%, P = 0.04). When analyzed by histologic sub-type, men were more likely to have papillary histology than women (17.4 vs. 4.5%), women were more likely to have chromophobe histology (11.2 vs. 5.0%; P = 0.006). Differences in demographics, pathologic parameters and histologic sub-typing are observed between men and women treated for renal masses.