Waterpipe smoking is popular in many parts of the world. Micronuclei (MN) evaluation in the exfoliated oral cells of smokers is a non-invasive technique for evaluation of possible tobacco harm. We aimed to assess whether MN levels are higher in waterpipe smokers than in never smokers. We examined oral smears of 128 adult male waterpipe smokers and 78 males who never smoked tobacco in rural Egypt. The total number of MN per 1000 cells per subject, and the number of MN-containing cells per individual were compared. We observed a higher level of total MN in waterpipe smokers (10 +/- 4) than in never smokers (4 +/- 2, p < 0.001). A similar difference was found for the mean number of affected cells per individual (8 +/- 3 vs. 4 +/- 1.62, p < 0.001). MN levels were not significantly dose related. This study is among the first to assess the association between waterpipe smoking and a cytogenetic measure of tobacco harm. The twofold increase in MN level is consistent with previous reports of MN in cigarette smokers. More research is needed to determine if such MN levels are predictive of future health consequences.