To investigate WWOX messenger RNA (mRNA) transcriptional levels in giant cell lesions (GCLs) of the jaws and associate its expression with clinical parameters.In this pilot study, quantitative reverse-transcription polymerase chain reaction was performed to analyze WWOX expression in 6 central giant cell lesions (CGCLs) (including 2 aggressive), 5 peripheral giant cell lesions (PGCLs) and 1 cherubism sample. Immunohistochemistry was performed to confirm the localization of the Wwox protein.CGCL and PGCL showed an overall increased expression of WWOX, as did the cherubism case, but no differences were observed among the groups. Wwox was localized almost entirely to the cytoplasm of multinucleated giant cells, as well as in a few mononuclear cells. CGCL and PGCL showed higher expression of the WWOX mRNA than peripheral blood mononuclear cells. The 2 aggressive CGCL samples exhibited decreased WWOX expression.These results showed increased expression of WWOX mainly in non-aggressive GCLs of the jaws.