Site-specific cancer trends are particularly useful indicators to identify cancers that should be subject to further case-control research to identify causes of the rate changes. One of the most sensitive of trends is that of the ratio of male-to-female rates, especially by age groups. This ratio is likely to eliminate rate changes due to better diagnosis, treatment, and cancer ascertainment. Also some lifestyle changes may be eliminated by considering the male-female ratio as they equally affect both genders. On the other hand, some may produce substantial effects. The finding of large increases in male-female cancer mortality ratios at specific sites in the United States and in all cancers, except lung, in several countries suggests that case-control studies of some sites are worthy of consideration to identify the gender-related differences. Because most male rates are increasing relative to females, any case-control study should certainly include occupational factors among those investigated.