BACKGROUND The purpose of the current study was to examine the screening histories of women diagnosed with invasive cervical cancer (ICC) in 2000 who had previous Papanicolaou (Pap) smears deemed to be unsatisfactory or with low-grade findings that did not lead to biopsy. METHODS A total of 252 Pap smears from 47 women taken between 1992 and 2000 were included in the study; 247 smears were reexamined at the laboratory of origin before the study and all 252 were then reexamined independently by 2 experienced cytotechnicians and 2 cytopathologists. RESULTS Of the 47 cases of ICC, 35 were squamous cell carcinoma, 10 were adenocarcinoma, and 2 were other types. On reexamination at the laboratory of origin, 24 cases were upgraded and in the study group 27 cases were upgraded to diagnoses requiring biopsy. On reexamination at the laboratory of origin, it was found that the first high-grade squamous intraepithelial lesion (HSIL) could have been diagnosed on average 4.2 years earlier than it was originally (95% confidence interval [95% CI], 3.3-5.1 years). On reexamination by the study group the first diagnosis of HSIL was made in smears dating from 5.4 years before the diagnosis of ICC (95% CI, 4.5-6.2 years). CONCLUSIONS The study confirms that unsatisfactory and low-grade Pap smears imply a risk of developing high-grade lesions at a later date and shows that in a screening program a subgroup of smears may be diagnosed as unsatisfactory or low grade despite the presence of high-grade findings that are detectable on reexamination.