The Family-Cancer Database was constructed from the nationwide Swedish registries to include more than 30,000 cancers in offspring diagnosed at ages 15-51 years and their parents. Cancer risk in the offspring was increased about 1.10 times when the father had cancer, whereas no increase was noted when the mother had cancer. If both parents had cancer, the risk for sons was 1.39 and for daughters, 1.34. Familial aggregation between parents and offspring was observed for 5 concordant and 14 discordant cancer sites and 10 parental sites at which all cancer was increased in the offspring. The concordant sites between the parent and offspring were colorectum, breast, melanoma, skin (squamous cell carcinoma), and thyroid. The aggregation at discordant sites in the parents and the offspring included stomach-breast, colorectum-salivary glands, colorectum-breast, colorectum-lymphoma, colorectum-leukemia, liver-breast, pancreas-breast, breast-melanoma, ovary-breast, prostate-breast, prostate-cervix, prostate-multiple myeloma, kidney-melanoma, and nervous tissue-melanoma. In most of these combinations, cancer in the second parent increased the risk to the offspring. The present results on young and middle-aged adults suggest that cancer in both parents increases cancer risk in the offspring at many sites. Chance and environmental effects may explain some of the results, whereas true genetic factors probably contribute to most of the findings. The molecular genetic explanation may be that rare dominant single genes increase susceptibility at many sites or that overlapping sets of genes control susceptibility at multiple sites.