The emergence of drug-resistant Candida albicans in immunocompromised patients is common. A disconcerting aspect of this phenomenon is the rapid emergence of C. albicans strains that are resistant to a widely used azole drug, fluconazole (FLZ). To understand the origin of FLZ-resistant yeast isolates, we investigated molecular profiles of 20 geographically related oral C. albicans isolates using three genotyping methods: randomly amplified polymorphic DNA-PCR, with six different primers (OBU1, OBU2, OBU3 RSD6, RSD11 and RSD12); electrophoretic karyotyping by pulsed-field gel electrophoresis; and HinfI restriction fragment analysis. Of the 20 isolates studied, 10 were FLZ- resistant and originated from patients with oral candidosis with a history of FLZ therapy, and the remainder were FLZ susceptible from individuals with oral candidosis, but without a history of FLZ therapy. A composite genotype was generated for each strain by combining molecular types derived from the three independent molecular methods. The composite profiles indicated genetic diversity amongst both the FLZ-resistant as well as -sensitive isolates, and no specific features emerged distinguishing the drug-resistant and -sensitive groups. These observations cast doubt on the theory of a clonal origin of FLZ-resistant C. albicans isolates.