Cancer occurrence in patients with multiple sclerosis (MS) has been little studied, but associations with brain tumours, breast cancer, Hodgkin lymphoma and nasopharyngeal carcinoma have been suggested. We took advantage of population-based registers of MS and cancer to assess the risk of cancer following diagnosis of MS. Patients registered in the Danish Multiple Sclerosis Register were linked with the Danish Cancer Register to obtain information on cancer occurrence. The ratio of the observed to the number of expected cancers based on population-based incidence rates, i.e., the standardised incidence ratio (SIR), served as measure of the relative cancer risk. A database comprising all Danish women born after April 1, 1935, with information on all live-born children, was used in the analyses of breast cancer to adjust for reproductive factors. Overall 1,037 cancers were observed in 11,817 MS patients during 153,875 person-years of follow-up vs. an expected number of 1,098 (SIR = 0.94 [95% confidence interval CI: (0.89–1.00)]. The risk of brain tumours and Hodgkin lymphoma was not increased. A 16% overall reduced cancer risk in men with MS was explained by reduced numbers of cancers of the digestive, respiratory and genital organs. Though the overall cancer risk was not increased [SIR = 1.01(0.94–1.09), n = 676], female MS patients had an increased risk of breast cancer [SIR = 1.21 (1.05–1.39), n = 193]. Adjusting for parity and age at first child delivery did not change this risk estimate materially. In general MS patients are not at increased risk of cancer. Women with MS, however, seem to have a small excess risk of breast cancer, which cannot be attributed to reduced parity or delayed first child birth. © 2005 Wiley-Liss, Inc.