In humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962-8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.