Background: The objective of this study was to estimate DNA image cytometry (DNA-ICM) as a first-line diagnostic method for diagnosis of cervical precancer with respect to its clinical behaviour. Methods: 30 consecutive patients with Papanicolaou smears that yielded diagnoses of LSIL or HSIL and showed single cell or stem line aneuploidy were included in a prospective cohort study. Slides were classified according to the Bethesda system. DNA-ICM was performed according to the consensus reports of the European Society of Analytical Cellular Pathology. Results: 24 (80%) patients with DNA aneuploid cervical epithelial cell abnormalities had cervical intraepithelial neoplasia (CIN) (CIN I: n = 5; CIN II: n = 6; CIN III n = 13). Six (20%) patients showed no evidence of CIN in subsequent biopsies. During follow-up of three years none of the six patients with negative histology developed cervical precancer or cancer. All 24 (100%) lesions confirmed as CIN by histology showed DNA aneuploidy in cytology. Conclusions: DNA-ICM should be used as an objective first-line diagnostic tool for predicting cervical precancer. Yet, due to immune response, DNA aneuploid cervical cell abnormalities do not seem to be enough to predict the definitive clinical outcome in each patient.