Aberrant expression of the cell surface adhesion molecule CD44 and its variant forms has been shown to be associated with the invasive and metastatic potential of cancer cells, and with poor prognosis in several types of cancers. Expression of CD44 standard (CD44s) and variant (CD44v) forms in oral squamous cell carcinoma (SCC), epithelial dysplasia (ED), epithelial hyperkeratosis (EH) and normal buccal mucosa (NBM) have been examined using antibodies to CD44s, CD44v5, CD44v6 and CD44v7-8. Positive CD44s, CD44v5, CD44v6 and CD44v7-8 staining was detected in all the specimens from NBM, EH and ED. Positive staining of CD44s, CD44v5, CD44v6 or CD44v7-8 was detected in 55 (88.7%), 48 (77.4%), 59 (95.2%) and 22 (35.5%) of the 62 SCC specimens, respectively. The positive staining of CD44v7-8 in oral SCC was significantly less than that in NBM (P<0.01). No significant correlation was found between CD44v7-8 expression and daily or total consumption of betel quids or cigarettes by the SCC patients. The 5-year survival rate for patients with CD44v7-8-positive tumours was significantly higher than that for the CD44v7-8-negative group (P<0.03). These results indicate that loss of CD44v7-8 expression may be a valuable factor for determining prognosis in oral SCC patients.