The aim of the study was to determine the incidences of anal cancer and high-grade anal intraepithelial neoplasia (AIN2/3) over time in Danish women and men. Describing the burden of anal cancer and AIN may be valuable in future evaluations of the human papillomavirus (HPV) vaccine. We included all anal cancers in the Danish Cancer Register in the period 1978-2008 and all cases of AIN2/3 in the Danish Registry of Pathology. Overall and age-, period- and histology-specific incidence rates were estimated. During the 30-year period, 2187 anal cancers were identified, two thirds of which were in women. Between 1978-1982 and 2003-2008, the age-standardized incidence rate of anal cancer increased from 0.68 to 1.48 per 100 000 person-years in women and from 0.45 to 0.80 per 100 000 person-years in men. Although there is no systematic screening for AIN in Denmark, we nevertheless identified 608 cases of AIN2/3 during the study period. The average annual percentage change of 5% between 1998 and 2008 represents a steep increase in the incidence of AIN in both genders. Furthermore, the incidence rate of HPV-associated anal cancers increased significantly, whereas that of non-HPV-associated histological types levelled out or even declined during the 30 years of observation. In women, the increase in HPV-associated cancers was more pronounced among those under 60 years of age. Our findings indicate that vaccines against HPV might play an important role in the prevention of anal cancer and its precursor lesions. © 2011 Wiley-Liss, Inc.