Prostate cancer (PC), in Iran, is the third most frequently diagnosed visceral cancer among men and the seventh most common underlying cause of cancer mortality. We evaluated the relation between speculated factors and PC risk using data from a multicentric case-control study conducted in Iran from 2005 to 2007 on 130 cases of incident, clinicopathologically confirmed PC, and 75 controls admitted to the same network of hospitals without any malignant disease. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression models. The risk of PC was increased with aging (OR: 5.35, 95% CI: 2.17-13.19; P<0.0001), and with the number of sexual intercourse >or=2 times/week (OR: 3.14, 95% CI: 1.2-8.2; P=0.02). One unit elevation in serum estradiol and testosterone concentration was related to increase (OR: 1.04, 95% CI: 1.01-1.06; P=0.006) and decrease (OR: 0.79; 95% CI: 0.64-0.96; P=0.02) of PC risk, respectively. Cases were less likely to have a history of diabetes (OR: 0.34, 95% CI: 0.12-0.98; P=0.04). Increasing in dietary consumption of lycopene and fat was associated with declined (OR: 0.45, 95% CI: 0.09-2.12) and increased (OR: 2.38, 95% CI: 0.29-19.4) PC development, respectively. Other factors including educational level, marriage status, dietary meat consumption, vasectomy and smoking have not been shown to affect PC risk in the Iranian population. Our study adds further information on the potential risk factors of PC and is the first epidemiologic report from Iran. However, justification of these results requires more well-designed studies with a larger number of participants.