In this retrospective study we have investigated the expression of Ki-67 and p53 in 175 random cases of cutaneous squamous cell carcinomas by using the monoclonal antibodies MIB-1 and DO-1, respectively. The expression of these antibodies was compared with various histological parameters of prognostic significance. The staining results were also compared with the clinical outcome of the patients. MIB-1 and DO-1 staining showed statistically significant correlation with histopathological grade of the tumor (p < 0.0001 and p = 0.0016, respectively). The degree of immunolabelling of these antibodies also showed significant correlation with tumor depth and tumor thickness (MIB-1 thickness p = 0.02 and depth p = 0.026, and DO-1 thickness p = 0.014 and depth p = 0.005). The majority of the squamous cell carcinomas in our series were Clark's level IV, which therefore did not correlate with the extent of immunoreactivity (MIB-1, p = 0.098; and DO-1, p = 0.885). Mean length of clinical follow-up was 5.2 years. Aggressive tumor behaviour was seen in 17 patients (10.6%) with 6.9% and 3.4% local recurrences and nodal metastasis respectively. A total of 89.4% patients remained disease-free following their definitive surgical treatment. Vulval skin represented the commonest site associated with unfavourable clinical outcome (five of 17 cases). A large number of squamous cell carcinomas in this poor prognosis group showed a high prevalence of immunoreactivity of the antibodies but this did not achieve any statistical significance. We conclude that Ki-67 and p53 expression in cutaneous squamous carcinoma is not an independent predictor of prognosis.