Low-grade cervical squamous intraepithelial lesions have a high rate of spontaneous regression but may undergo surgical treatment (cone biopsy) in case of persistence of the lesion or discrepancy between Pap-smear diagnosis and biopsy diagnosis. This may sometimes lead to surgical complications and/or adverse effects on fertility. Thus, the present study was designed to investigate the potential of laminin-5 as a sensitive molecular marker identifying cervical intraepithelial neoplastic lesions (CIN), which are likely to regress and ultimately spare women unnecessary surgical procedures. Cervical punch biopsy samples from 65 women with either a CIN I or a CIN II were evaluated for the expression of laminin-5 by immunohistochemistry. All study subjects agreed to a conservative clinical management and were frequently followed-up (median follow-up time 237 days) to evaluate for changes in the dysplastic lesion. Laminin-5 staining results were correlated with patient's characteristics as well as clinical follow-up data. Laminin-5 expression was detected in 16 of 40 CIN I (40%) lesions, 2 of 21 CIN II (9.5%) lesions and none of 4 reclassified CIN III lesions. Within positive cases, laminin-5 expression was localized to the cytoplasm of the dysplastic cells. The laminin-5 expression was significantly associated with the grade of CIN lesion (p < 0.005). Correlations with patient's characteristics were not statistically significant except for education and ectocervical smear diagnosis. No significant associations were noted between laminin-5 expression and either regression, persistence or progression of the CIN lesions. These data indicate that laminin-5 is not a useful diagnostic adjunct in histopathology for the identification of CIN lesions with progressive capacity.