A 6-year follow-up study of 44 primarily enucleated odontogenic keratocysts from 13 patients with the characteristic signs and symptoms of the nevoid basal cell carcinoma syndrome (NBS) is presented. The 2-, 3-, 4-, 5- and 6-year follow-ups revealed an incidence of recurrence by the single keratocyst of 20, 30, 39, 50 and 55 %, respectively. These figures demonstrate that the majority of the recurrences occurred within a period of 5 years postoperatively. However, as the proportion of increased recurrence in the period from 5 to 6 years postoperatively was 5 %, a follow-up period of more than 6 years is necessary in order to make the diagnosis of recurrence without any delay in all patients with NBS. The occurrence of odontogenic epithelium and/or microcysts in the cyst wall of keratocysts without any recurrence at the 5-year follow-up was compared with the occurrence of similar histopathologic features in keratocysts which at the 5-year follow-up had shown recurrence. The occurrence of odontogenic epithelium and/or microcysts was demonstrated in 43 % of the group of keratocysts without recurrence and in 57 % of the group of keratocysts with recurrence. However, this difference is not statistically significant (P > 0.10) and indicates that the high occurrence (50 %) of odontogenic epithelium and/or microcysts in NBS-keratocysts is not significantly correlated to the recurrence.