Each year, an estimated 2 to 3 million women in the United States receive a Papanicolaou smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). There is no uniform practice for the diagnosis or management of these patients, and the annual cost of aggressively treating ASCUS lesions is estimated to be billions of dollars. Since its introduction in 1988, ASCUS has been problematic and controversial. ASCUS is a problem to define, to diagnose, to reproduce, and to manage. The following article reviews the various aspects and problems of ASCUS, its controversies regarding diagnosis, reproducibility, and management, and discusses the possible future directions of this category in light of the recent Bethesda System 2001 Workshop recommendations.