Rosselli-Gulienetti syndrome (RGS) is an inherited genetic disease, follows an autosomal recessive pattern of inheritance. This is a case of completely edentulous RGS with incomplete closure of the roof of the mouth and a cleft lip with an oronasal communication. The presence of an oronasal fistula presents a challenge to maxillary complete denture fabrication because leakage of air from the nasal cavity through the fistula prevents the formation of an adequate border seal and further absence of an anterior portion of alveolar ridge and lip, worsen the retention of the denture. The overall goal of rehabilitating such patients is focused on the closure of oronasal communication, improving acceptable speech, appearance, proper occlusion, and masticatory function. The present clinical report illustrates an alternative solution by integrating a small retentive component into a maxillary complete denture.