Endometrial cancer was studied in the Swedish Family-Cancer Database, updated in 1999 to cover individuals born after 1934 with their biological parents, totaling 9.6 million persons. Cancer data were obtained from the Swedish Cancer Registry from 1958 to 1996 and included over 20,000 cases of endometrial cancer. Seventy-six families were identified in which both the mother and the daughter had endometrial cancer, giving a familial standardized incidence ratio (SIR) of 3.19 for daughters and 2.78 for mothers. The risk depended inversely on the age at diagnosis, and the risk was almost 10 in daughters who were diagnosed before age 50 when their mothers were also diagnosed before that age. The discordant cancer site that associated with endometrial cancer between the two generations was colon, with a SIR of 1.44-1.68. However, when the maternal endometrial cancer was diagnosed before age 50, increased SIRs were observed in daughters or sons for rectal, pancreatic, nervous system, breast, and ovarian cancers. Second cancers were followed in females diagnosed with endometrial cancer, and the highest overall risks were observed for ovarian and connective tissue cancers; colorectal cancers were also clearly in excess. Among the other family members of the 76 families in which both mother and daughter were affected with endometrial cancer, there were 11 cases of colorectal cancer. When a sister was affected in such families, the SIR of endometrial cancer was 31.40, and the median diagnostic age was several years lower than in endometrial cancer families in which no colorectal cancers were found. Many of these families may have hereditary nonpolyposis colorectal carcinoma syndrome. However, the risk of endometrial cancer was increased even in families presenting no colorectal cancers.