The incidence of anal cancer is increasing in the general population among both men and women. The incidence is particularly high among men who have sex with men and HIV-infected men and women. Anal cancer is similar to cervical cancer and is associated with human papillomavirus (HPV). Anal cancer is potentially preventable through primary prevention with HPV vaccination or secondary prevention. Secondary prevention is modelled after cervical cancer, where cytology is used as a screening tool to identify women who need colposcopy. Colposcopy includes magnification of the cervix, which, along with acetic acid and Lugol’s solution, is used to visualise and biopsy potentially precancerous lesions, enabling treatment before progression to cervical cancer. Anal cancer is likely preceded by high-grade anal intraepithelial neoplasia (HGAIN), and a colposcope with acetic acid and Lugol’s solution may similarly be used to visualise HGAIN to permit biopsy and treatment in an effort to prevent anal cancer. To distinguish it from cervical colposcopy, this technique is called high-resolution anoscopy (HRA). Many of the features that distinguish low-grade AIN from HGAIN are similar to those of the cervix, but HRA poses several additional challenges compared with cervical colposcopy. These include uneven topography; obscuring of lesions due to haemorrhoids, folds, stool or mucus; or lesions being located at the base of folds and anal glands. Consequently, a long learning curve is typically required before becoming fully competent in this technique. The technique of HRA, its uses and challenges in prevention of anal cancer are described in this article.