Analysis of familial cancer risks between discordant sites provides etiologic understanding on genetic and environmental risks factors of site-specific cancers. We used the Swedish nation-wide Family-Cancer Database to analyze familial risks in discordant cancers of offspring and parents. Familial risk ratios (FRRs) were calculated for cancer in offspring aged 15 to 53 years at 22 sites, discordant from parental sites. We confirmed many reported associations. Consistent novel findings associated parental-offspring sites of pancreasbreast, breast-testis and uterus-nervous system. For these, the FRRs were modest, 1.2 to 1.5 in the whole Database, but the FRRs increased in those whose parents were diagnosed before age 50. Pancreas and liver cancers showed FRRs of 2.5 to 3.3 in offspring of women and of 1.3 in offspring of men. One or both of these cancers was/were associated with cancers of stomach, colon, breast, uterus, ovary and prostate. Melanoma was associated with pancreas, breast, skin and nervous-system cancers and with leukemias. Myeloma showed a concordant FRR of about 4.0 and was associated with prostate cancer and non-thyroid endocrine-gland cancers. Mutations in known cancer-related genes may explain some of these findings, but new susceptibility genes are yet to be found. For melanoma, pancreatic and liver cancer, environmental factors are important etiologic factors and may contribute to the familial effects observed. Int.