OBJECTIVE: To evaluate whether ThinPrep smears without versus those with a transformation zone component were more likely to have falsely negative cytology findings. METHODS: Women aged 18-50 (N = 4389) attended one of three Planned Parenthood clinics between 1997 and 2001 for screening by ThinPrep Papanicolaou and polymerase chain reaction-based human papillomavirus (HPV) DNA testing. Women with 1) any cytologic abnormality, 2) high-risk HPV types, and 3) a random sample with normal Papanicolaou and negative HPV tests were offered repeat cytology, colposcopy, and biopsy. Cytology and biopsy diagnoses at the colposcopy visit were reviewed according to the presence (n = 3689) or absence (n = 700) of a transformation zone component at screening. RESULTS: Among women with normal cytology at screening, histologic detection of at least cervical intraepithelial neoplasia grade 2 (odds ratio 1.3, 95% confidence interval 0.5, 3.3) at colposcopy did not differ significantly between transformation zone-positive and zone-negative smears. Histologically confirmed cervical intraepithelial neoplasia grade 1 was detected more often among smears lacking a transformation zone component (odds ratio 2.0, confidence interval 1.0, 3.8). Transformation zone-negative smears were more common among older women, current oral contraceptive users, those past the 14th day of their last menstrual period, and those negative for high-risk HPV types. CONCLUSION: Absence of a transformation zone component in a screening ThinPrep Papanicolaou test was not associated with missed high-grade lesions. Based upon our data, we do not recommend repeat screening of reproductive-aged women with negative liquid-based tests and no cytologic evidence of a transformation zone component.