Background: Insulin-like growth factor-۱ can act in both an autocrine and paracrine manner to promote normal growth and malignant cellular proliferation. The importance of this factor as a major regulatory peptide has been established for cells, in vitro and in vivo. However, the role of serum insulin-like growth factor-۱ levels in the etiology of benign prostatic hyperplasia and prostate cancer has not received sufficient attention. The aim of this study was to determine the relationship between benign prostatic hyperplasia, prostate cancer, and serum insulin-like growth factor-۱ levels. Methods: We collected blood samples from ۶۸ individuals with prostate cancer (cases) and ۶۸ individuals with benign prostatic hyperplasia (controls) who were patients at Imam Khomeini Hospital in Tehran, Iran. Those with benign prostatic hyperplasia had normal prostatic specific antigen levels Results: Patients in the prostate cancer group had a mean age of ۶۸ years, whereas those with benign prostatic hyperplasia had a mean age of ۶۵ years (P>۰.۰۵). Mean serum insulin-like growth factor-۱ levels were ۲۱۹ ng/ml for the case group and ۱۳۳ ng/ml for the control group, which was significant (P=۰.۰۰۰۹). We did not observe any correlation between age and insulin-like growth factor-۱ in the case group (P=۰.۸۳, r= -۰.۴۷), however there was a significant correlation in the control group (P=۰.۰۰۷, r=۰.۵۴۹). Although correlation between prostate volume and serum insulin-like growth factor-۱ levels was not statistically significant in the case group (P=۰.۳۸, r=۰.۲۱۳), there was a positive correlation observed in the control group (p <۰.۰۰۸, r=۰.۵۳۷). Conclusion: Our findings suggest that insulin-like growth factor-۱ may have an etiologic role in prostate cancer. This interpretation is strengthened by the significant difference observed between serum insulin-like growth factor-۱ levels in benign prostatic hyperplasia and prostate cancer patients. These results also offer additional opportunities for evaluating patients who have abnormal digital rectal exams or prostate specific antigen levels, yet their biopsies are normal. Under these circumstances, measurement of serum insulin-like growth factor-۱ may assist with the decision for a second biopsy.