Cervical cytology screening has a long history and has successfully reduced the impact of cervical cancer in many countries. Anal cytology is a relative newcomer and anal screening is currently offered in only a few centres around the world. Many questions need to be answered before anal screening is more widely adopted. While there are many similarities between cervical and anal squamous cell carcinoma, there are also important differences: differences in the prevalence of disease, in the 'at-risk' target populations and possibly in the robustness of the reference standard of biopsy. The performance of cytology as a screening test in the literature varies widely but it is essential to understand that some of this variability is due to differences in the definitions of key parameters in the various studies. For cervical screening, estimates of sensitivity have ranged from 19% to 94% and specificity from 94% to 98%. For anal screening, data are fewer and more limited. Estimates of the sensitivity of anal cytology in men who have sex with men and HIV-positive populations have ranged from 55% to 87% and specificity from 37% to 76%. Ultimately, rather than comparing anal with cervical cytology, it may be more helpful to assess the value of anal cytology independently through well designed trials.