Objective: It was the aim of this study to evaluate the significance of reporting hyperkeratosis in cervical smears. Study Design: Cervicovaginal smears with low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), prepared from 2004 to 2007, were retrospectively reviewed. Anucleated squamous cells were counted. The smears were classified into two groups, based on the presence of <2 or ≥2 clusters of anucleated cells, and then compared. Results: Sixty Pap smears showing SILs (34 LSILs and 26 HSILs) as well as 120 random satisfactory smears without squamous or glandular abnormalities were selected. A statistically significant difference was found between the SIL group and the control group regarding the mean number of hyperkeratotic clusters (2.8 in the SIL and 1.9 in the control group; p = 0.012). Moreover, the mean number of hyperkeratotic clusters (3.3 in the LSIL and 2.2 in the HSIL group) had a statistically significant correlation with the diagnosis of the lesion as LSIL or HSIL (p = 0.0006). Conclusion: Our findings suggest that hyperkeratosis in the form of ≥2 clusters of anucleated squamous cells could be an indicator of underlying LSIL.