Purpose: To determine the underlying pathology and clinical significance of epithelial cell abnormalities (ECA) identified during cervical Papanicolaou (Pap) smear screening. Material and Methods: A total of 19,215 Pap smears stained by Papanicolaou stain were screened during a 36-month period. They were classified according to The Bethesda System (TBS) for cervical cytology screening and the results of ECA were compared with histology. The chi square test was applied to determine the significance and validity of high-grade lesions on cytology diag­nosis. Result: 360 cases of ECA were identified. Mean age at presentation was 50.58 years. Cytohistologic correlation of ECA was pos­sible in n = 249 (69.17%) of cases. Out of these, 18 cases were negative, six were inflammatory, three were benign, and 222 cases showed pathology ranging from mild dysplasia to invasive carcinoma. The chi square test showed a highly significant predictive value (p < 0.001) for high-grade lesions detected on Pap smears. Conclusion: Pap smear results of high-grade squamous intraepithelial lesions (HSIL) or invasive malignancy are highly reliable and the patient may be considered directly for therapeutic intervention. Of cytologically detected ASCUS cases 38.89% were diag­nosed as CIN (1-3) on histology. Thus the management of these patients needs to be re-evaluated. Atypical glandular cells of unde­termined significance (AGUS) detected in postmenopausal women signify an underlying pathology. These patients should be further investigated and followed to biopsy if necessary.