Phytoestrogens are natural estrogen-like plant substances. The possible protective effect of phytoestrogens on cancer risk, particularly on hormone-related cancers, has been the focus of many epidemiologic studies during the last 2 decades. We performed a qualitative review of the epidemiologic literature published in the English language and identified on MEDLINE from 1966 until 24 September 2006 on (1) dietary intake of soy, isoflavones, or lignans; (2) urinary excretion of isoflavones or lignans; (3) blood measurements of isoflavones or lignans in relation to breast, prostate, and endometrial cancer risk. Epidemiologic data do seem to support a small protective effect of isoflavones on breast cancer risk, although timing of exposure and the mechanisms of isoflavones at physiologic levels need to be further explored. The epidemiologic evidence to date is conflicting regarding lignans and breast cancer, but recent studies suggest that the effect may be restricted to premenopausal women, differ by estrogen receptor status, and be modified by diet-gene interactions. The 3 case-control studies on dietary intake of phytoestrogens and endometrial cancer risk have provided some evidence for a protective effect, but more prospective data are needed. There is some epidemiologic evidence for a protective effect of soy or isoflavones on prostate cancer, but corresponding data for lignans are inconclusive. Recent data indicate that diet-gene interactions may modify the effect of phytoestrogens on prostate cancer risk. Prospective studies on dietary lignans in relation to prostate cancer risk are lacking.