There is increasing evidence that vitamin D reduces the risk of many types of cancer. Geographic variations in cancer mortality rates in Spain are apparently linked to variations in solar ultraviolet (UV) irradiances and other factors. Cancer mortality rates for 48 continental Spanish provinces for 1978-1992 were used in linear regression analyses with respect to mortality rates for latitude (an index of solar UVB levels), skin cancer (an index of high cumulative UVB irradiance), melanoma (an index related to solar UV irradiance and several other factors) and lung cancer (an index of cumulative effects of smoking). The 9 cancers with mortality rates significantly correlated with latitude for 1 or both sexes were brain, gastric, melanoma, nonmelanoma skin cancer (NMSC), non-Hodgkin's lymphoma (NHL), pancreatic, pleural, rectal and thyroid cancer. Inverse correlations with latitude were found for laryngeal, lung and uterine corpus cancer. The 17 cancers inversely correlated with NMSC are bladder, brain, breast, colon, esophageal, gallbladder, Hodgkin's lymphoma, lung, melanoma, multiple myeloma, NHL, ovarian, pancreatic, pleural, rectal, thyroid and uterine corpus cancer. The 16 correlated with melanoma are bladder, brain, breast, colon, gallbladder, leukemia, lung, multiple myeloma, NHL, ovarian, pancreatic, pleural, prostate, rectal, renal and uterine corpus cancer. The results for lung cancer were in accordance with the literature. These results provide more support for the UVB/vitamin D/cancer hypothesis and indicate a new way to investigate the role of solar UV irradiance on cancer risk. They also provide more evidence that melanoma and NMSC have different etiologies. ' 2006 Wiley-Liss, Inc.Key words: cancer; ecologic; melanoma; skin cancer; smoking; Spain; ultraviolet; vitamin D Evidence continues to mount that vitamin D produced from solar ultraviolet B (UVB) irradiance or taken orally reduces the incidence and mortality rates of and increases the survival for many forms of cancer. The UVB/vitamin D/cancer hypothesis was originally proposed in 1980 with respect to colon cancer 1 and has now been extended to about 20 types of cancer 2-4 including melanoma 5,6 and non-Hodgkin's lymphoma. 7,8 Although much of the research linking vitamin D to cancer risk reduction is observational, there is sufficient supporting evidence for mechanisms, 9,10 dose-response relationships, 3,11 replications in diverse populations 12,13 and seasonal variations in cancer survival rates 14-18 that the criteria for causality in a biological system 19 are generally satisfied if not fully accepted. One of the objections is the use of latitude as an index of solar UVB irradiance and vitamin D production in ecologic studies.Spain has an excellent mortality rate dataset for 30 types of cancer for 52 provinces, spanning 1978-1992. 20 Such data would be useful in trying to learn more about the causes of cancer 21 and have been used in previous studies to investigate the geographic variation in cancer mortality rates with respect to such f...