A clinicopathological study of OSSN has not previously been performed in Malawi. The association of HIV with SCC corresponds to previous reports from sub-Saharan Africa. A new finding in our study is a relationship between larger tumour size and invasive lesions confirmed by histopathology. When integrated into a clinical decision-making model, tumour area provides a simple clinical measure for ophthalmic practitioners to use in order to differentiate higher risk OSSN from more benign pathology. The higher risk lesions can subsequently be treated with greater surgical care and undergo closer follow-up.