We present here a case of a patient with Gorlin-Goltz Syndrome treated and followed up for more than 22 years. During the evolution of the disease, we have noted a severe development of symptoms that necessitated the resection of multiple face and trunk basalioms, as well as numerous maxillary keratocysts. One of the cysts has presented the histologic characteristics of an ameloblastic fibroma. Later on, the growth of a squamous cell carcinoma required a partial mandibular resection, primary reconstruction (with AO-plate) and postoperative radiotherapy. Afterwards, a relapse in the symphysar region necessitated, in spite of the presence of lung metastases, another resection of the same region including part of the lower lip with secondary reconstruction by the means of a myocutaneous flap (PMM). A review of the main features of this syndrome has been carried out. With the help of a literature review, all the similar cases already published are here presented and discussed. Furthermore, our therapeutic concept concerning this syndrome is briefly discussed.