Abstract Purpose The purpose of this work is to describe the peculiarities of clinical and radiological behavior in SCCs arising from odontogenic cyst (PIOSCC). Material & methods Our computer based records were retrospectively reviewed looking for patients who underwent radical surgery for PIOSCC from December 2001 to January 2016 with a minimum post-operative follow-up of 2 years. Information obtained from radiological findings and treatment outcome were collected. Results From 2001 to 2016, 6 out of 560 SCC's patients (1,07%) were diagnosed PIOSCC. 5 females and 1 male, mean age was 55,2 years (range, 28–82 years). 4 PIOSCC were located in the mandible while 2 in the maxilla. Orthopantomography (OPT) has not given specific signs of malignancy. CT methods (msCT/CONE BEAM-CT/contrast-enhanced CTs) provided more information: unilocular lesions with multiple and excessive cortical interruptions, periosteal reaction far beyond the lesion in all directions, dislocation or disappearance of the IAN, intense peripheral remineralization. In all cases, the treatment involved incisional biopsy of the suspect lesions and subsequent surgical excision of the primary tumor with neck dissection in continuity in the mandibular PIOSCC and in discontinuity in PIOSCC of the maxilla. Recurrence or distant metastases was not observed until now (follow-up from 48 months to 168 months) Conclusions Carcinomas on cysts have radiological "red flag" characteristics (bone erosion, large dimension, involvement of IAN..) that must be taken into consideration in order to perform an early diagnosis and a correct treatment. Accurate radiological study can reduce misdiagnosis and improper treatment. PIOSCC have a progression of the disease and a different prognosis from real intraosseus carcinomas (PIC) and although it is a rare entity it must be considered in the differential diagnosis of larger osteolytic lesions
