Objective: The evaluation of postmenopausal Pap smears can often be challenging. Degeneration associated with atrophic vaginitis, hyperchromatic crowded groups, parabasal cells with organophilic cytoplasm or variations in nuclear size may be falsely interpreted as squamous atypia or even more severe lesion. Method: The study included 25 postmenopausal Papanicolaou patients (26 smears) with the initial cytological diagnosis of ASC-US or ASC-H. The smears were decolorized and immunostaining for p16(Ink4a) was applied. In 21 patients (22 smears) tissue biopsy and histological examination was performed and four ASC-US cases had cytological follow up only. Results: Among cases with histological examination positive p16 reaction was found in 17 patients (18 smears). The histological diagnoses were: CIN1 (3), CIN 1-2 (2), CIN2 (1 case), CIN3 (5 patients/6 smears), AIS (1 case) and invasive squamous carcinoma (2 patients). Two p16 positive patients with three smears and initial negative histology had CIN3 after 2 years. Among p16 negative patients there were two with CIN3 and two with normal histology. Four ASC-US patients without histological examination had normal cytological follow up. Conclusion: P16 is a useful marker in detecting of clinically significant cervical lesions in postmenopausal women.