Background Diffusion-weighted imaging obtained with magnetic resonance (DW-MRI) is a non-invasive imaging tool potentially able to provide information about microstructural tumor characteristics. Purpose To prospectively analyze the correlation between the apparent diffusion coefficient (ADC) and clinical-histologic characteristics of squamous cell carcinoma (SCCA) of the oral cavity and oropharynx. Material and Methods Sixty-seven patients with untreated, histologically proven SCCA of the oral cavity and oropharynx underwent conventional and diffusion-weighted (b-values 0, 50, 250, 500, and 900 s/mm²) MRI. Tumor ADC was calculated from regions of interest drawn manually on the highest b-value images using ImageJ (ImageJ, NIH) and fsl (fsl 4, University of Oxford) image processing packages. ADC was calculated in two ways: standard ADC using all b-values; and ADC^High using only b-values ≥ 250 s/mm². We assessed the correlations between both ADC and ADC^High and the clinical-histological characteristics of SCCA. Results Fifty-two patients (36 men, 16 women; mean age, 55 ± 13 years) were suitable for ADC calculation. Mean ADC was 1136.0 ± 108.5 × 10^–6 mm²/s. Mean tumor ADC^High was 991.2 ± 152.1 × 10^–6 mm²/s. Mean tumor size was 32.3 ± 13.4 mm (range, 14.0–69.0 mm). We observed no correlation of either ADC or ADC^High values with any of the clinical-histological tumor characteristics. Undifferentiated tumors (G3) showed lower apparent diffusion coefficient values compared to differentiated ones (G1-G2), without reaching statistical significance. Conclusion We did not observe any statistically significant correlation between ADC values and clinical-histological characteristics of SCCA of the oral cavity and oropharynx.