Background: Ichthyosis uteri is an uncommon entity in which the entire endometrium is replaced by stratified squamous epithelium. Though the condition often is considered as benign, dysplastic changes have been reported. Case: We describe herein an exceedingly rare case of primary squamous cell carcinoma of the endometrium (PSCCE) associated with extensive ichthyosis uteri with chronic pyometra, who presented with blood-stained vaginal discharge of six-seven months duration. Although repeated endometrial biopsies revealed only strips of stratified squamous epithelium showing moderate to severe dysplastic changes, the tumor markers and magnetic resonance imaging strongly suggested advanced uterine body malignancy. Exploratory laparotomy was performed, and histologic findings of the superficial layer were consistent with ichthyosis uteri; in contrast the lesion of invasive squamous cell carcinoma was located in the deeper layer and lymph nodes. No dysplastic changes of the cervix were noted. Conclusions: It is suggested that PSCCE could be associated with pre-existing ichthyosis uteri and deeper biopsies should be performed for the accurate preoperative diagnosis of cases with chronic pyometra.