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Glandular odontogenic cyst (sialo-odontogenic cyst) ( GOC) is an uncommon developmental odontogenic cyst. Its clinical significance lies in its tendency to recur, and histopathological features which mimic those of mucoepidermoid carcinoma ( MC). Molecular methods such as fluorescence in situ hybridisation ( FISH) have the potential to identify genetic abnormalities that are specific to MC and thus avoid this diagnostic pitfall. This report describes three cystic lesions of the jaws with a differential diagnosis of GOC and MC. One occurred in the mandibular premolar area of a 49-year-old woman and was diagnosed as GOC. The second developed in the maxilla of a man aged 39 in association with an impacted second premolar tooth. This was initially diagnosed as dentigerous cyst, but after recurrence 6 years later, the diagnosis was revised to GOC. The third occurred in the left retromolar area of a 30-year-old woman 5 years after the extraction of the left mandibular third molar; a diagnosis of GOC was favoured after two incisional biopsies, but a third showed unequivocal, invasive MC which had infiltrated nerves and bone. Morphologically, the only distinguishing feature was the so-called epithelial sphere, whorl or plaque-like thickening, which was identified in both GOC but not in the MC. FISH confirmed the above diagnoses by demonstrating a MAML2 rearrangement in the MC, but in neither of the GOC. While histopathology may reliably distinguish between GOC and MC, the presence of the specific MAML2 rearrangement in the latter clinches the diagnosis. [ABSTRACT FROM AUTHOR]