Early detection of OSCC is a crucial step towards improving OSCC prognosis. In recent years, novel diagnostic aids such as light-based detection systems have been introduced for early diagnosis. VELscope is one such light-based device which is used to examine tissue fluorescence. Based on different studies, VELscope has a sensitivity of 90% in the diagnosis of oral premalignant and malignant lesions. Tumor depth of invasion and invasive front have recently been proposed as influential factors in OSCC prognosis. Therefore, the aim of this study was to assess the relationship between tissue color seen through this device and tumor depth of invasion. 20 histopathologically approved OSCCs were included in this study. Conventional oral examination was carried out followed by an assessment of the lesion using VELscope. The H&E slides prepared following the final OSCC surgeries were then examined by an oral pathologist to assess tumor depth of invasion (interpreted as low-risk/high-risk), invasivefront (low-risk/high-risk) and perivascular and perineural invasions. Data was transferred to SPSS 16 software. The association between color changes and histopathological factors was analyzed using the fisher's exact and chi-square tests. The mean age of the patients was 51/5+/-16/74, 60% of which were men. Most lesions were exophytic and the most common color seen during VELscope examination was red. 55% and 50% of the OSCCs showed high-risk tumor depths and high-risk invasive fronts respectively. Perivascular and perineural invasion was seen in 55% and 35% of the samples respectively. Statistical analysis showed that 72/2% of the lesions with high tumor depths and 70% with high-risk invasive fronts were seen as red, although these associations were not significant (P>0/05). Tumor depth was significantly correlated with invasive front (P<0/05). There was no significant relationship between the type of color seen through VELscope and tumor depth of invasion, however most cases with high-risk depth of invasions were red.