Objective The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4 + , and CD8 + in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC). Materials and methods Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed. Results Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4 + cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8 + cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC ( p  = 0.05), whereas there were higher CD8 + cells levels in the carcinomas when compared with the OPML that evolved into carcinomas ( p  = 0.027). Conclusions CD8 + cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8 + cells than its associated OPML. Clinical relevance Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.