The study assessed the ability of Candida albicans isolates to invade an in vitro oral tissue model. The extent and pattern of isolate invasion was then correlated with the infection origin of the isolate to identify characteristics that may be restricted to specific forms of oral infection, particularly chronic hyperplastic candidosis (CHC). Reconstituted human oral epithelium was infected with C. albicans isolated from normal oral mucosa (n = 4), CHC (n = 7), non-CHC oral candidoses (n = 4) and squamous cell carcinoma (SCC; n = 4). After infection for 24 h, histological analysis revealed yeast adhesion, hyphal extension, and invasion of the epithelium. Differential patterns of invasion were evident and, whilst consistent for a given isolate, did not relate to the infection origin of the isolate. Two principal patterns of invasion were evident and described as either a 'localised' or a 'uniform' distribution of invading hyphae. Several isolates also exhibited superficial infection with limited hyphal invasion. In conclusion, the use of the in vitro tissue model allowed the assessment of the invasive capabilities of isolates of C. albicans. However, the apparent differences in invasive characteristics did not appear to be related to the clinical origin of isolates.