Odontogenic keratocyst of the mandible is a challenging pathology to treat in Oral and Maxillofacial surgery. Secondary infections in large Odontogenic Keratocyst can lead to histopathological misdiagnosis. In such cases final diagnosis is usually made after complete surgical enucleation. We faced similar situation in two cases which are reported in the article.Enucleation with open packing was used for their treatment and has been found to be a good conservative approach in its management.