To evaluate the variables possibly related to actinic keratosis and malignant skin lesions on the eyelid. A prospective study of patients with suspected eyelid malignancy was conducted. The participants underwent a 2-mm punch biopsy at two opposite sites of the lesion for diagnosis, and the results were compared with those of the histopathological study of the surgical excised specimen. The patients with an actinic keratosis component were divided into two groups (actinic keratosis-associated malignancy and actinic keratosis alone), which were compared for the following variables: age, disease duration, largest diameter, tumor area, Fitzpatrick classification, sex, tumor site and margin involvement. A cluster analysis was also performed. We analyzed 174 lesions, of which 50 had an actinic keratosis component. Actinic keratosis was associated with squamous cell carcinoma in 22% of the cases and to basal cell carcinoma in 38%, which shows that both neoplasms may have contiguous actinic keratosis. Statistical analysis revealed no significant difference among the variables. In a cluster analysis, four groups were identified with malignant lesions in the medial canthus with the largest mean diameter and area. All margin involvements on the lower eyelid were related to malignancy, which means that all cases with margin involvement had an almost 100% risk of malignancy. Larger actinic keratosis lesions in the medial canthus and lesions with margin involvement on the lower eyelid have a greater probability of malignant association.