A few twin studies on cancer have addressed questions on the possible carcinogenic or protective effects of twining by comparing the occurrence of cancer in twins and singletons. The nationwide Swedish Family-Cancer Database of 10.2 million individuals and 69,654 0- to 70-year-old twin pairs were used to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancers compared to singletons. The overall risk of cancer in same- or different-sex twins was at the same level as the risk for singletons. Testicular cancer, particularly seminoma, was increased among same-sex twins (1.54) and all twins to an SIR of 1.38. Among other tumors, neurinomas and nonthyroid endocrine gland tumors were increased. Colorectal cancers and leukemia were decreased among all twins. Melanoma and squamous cell skin cancer were decreased in male same-sex twins. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. In utero hormonal exposures or postnatal growth stimulation may be related to the risk of testicular cancer and pituitary tumors. Protective effects against colorectal cancer may be related to a beneficial diet, and in melanoma and skin cancer, to socioeconomic factors. The study involved multiple comparisons, and internal consistency between the results was one of the main factors considered for their plausibility. The results should encourage others working on twin and singleton populations to examine the specific associations and emerging hypotheses.