Heat shock proteins (HSPs) work as molecular chaperones that can assist cells to deal with stressful situations. Members of the HSP70 family can regulate cell growth and transformation and are involved in the maintenance of cellular homeostasis. In view of the distinct clinical behavior of odontogenic lesions, the objective of the present study was to investigate the immunohistochemical expression of HSP70 in these lesions. In this study, 70 formalin-fixed paraffin-embedded tissue blocks of odontogenic lesion-16 unicystic ameloblastomas (UAs), 17 solid ameloblastomas (SAs), 18 odontogenic keratocysts (OKCs), and 19 dentigerous cysts (DCs)-were reviewed by immunohistochemistry for HSP70 staining. In this study, HSP70 immunostaining was evident in all groups of the specimen. Mean percentage of HSP70 staining in SAs (84.2 ± 11.3) and OKCs (83.4 ± 6.8) were significantly higher than UAs (64.4 ± 9.8) and DCs (12.6 ± 10.2) (p = 0.00). But, there was no statistically significant difference between HSP70 expression in SAs and OKCs. The result of this study proposes that high expression rate of HSP70 has a role in the pathogenesis of ameloblastoma and OKC and is one of the reasons for the aggressive behavior of ameloblastoma and high recurrence role of OKC, reinforcing the classification of OKC as an odontogenic tumor.