Abstract The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman’s test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.