The aim of this study was to analyze the characteristics of 17 women with renal-cell carcinoma (RCC) associated with other primary neoplasms occurring in steroid-hormone target tissues. The reproductive history of these patients and the use of exogenous hormones were taken into consideration. In all, 10 RCCs were associated with breast carcinoma; 4, with endometrial carcinoma; and 3, with ovarian carcinoma. The presentation of a second primary tumor was described as synchronous or metachronous by evaluation of the interval between the discovery of the two neoplasms. Hormone and surgical treatment as well as pathologic findings for each primary tumor were also reported. In these 17 RCCs the overall rate of disease-specific survival recorded after a mean follow-up period of 32.7 months (range 9-66 months) was 58.8%; 7 patients died of metastatic disease after surviving for a mean of 14.7 months. In terms of the pathologic stage of RCC, a significant difference in mean survival was found between pN0 (mean survival 22.1 +/- 3.4 months) and pN1 RCCs (mean survival 13.7 +/- 3.5 months). A total of 13 (76.4%) women were postmenopausal at the time of diagnosis of the first primary tumor; the mean age of these women at menopause was 51.7 +/- 1.2 years. No prior use of oral contraceptives was reported by 12 (70.5%) of the 17 patients. Plasma 17-beta-estradiol and estrone levels were determined in only 7 patients at the diagnosis of each of the primary tumors. High plasma estrogen levels were found in 4 women with RCC and breast carcinoma and in 1 patient with RCC and endometrial carcinoma; in the remaining 2 patients low-normal values were found. A relationship appears to exist between certain reproductive and hormone-related factors and the risk of developing these tumor associations. Data emerging from the present study do not provide strong support for the hypothesis of hormone dependency of RCC; however, a role for estrogens in cases in which RCC is associated with other primary tumors involving steroid-hormone target tissues can be hypothesized.