The origins and mechanisms of pain arising from oral cancer are important. Oral cancer pain impairs a patient's quality of life. This study was undertaken to elucidate significant risk factors associated with spontaneous pain in patients with untreated oral squamous cell carcinoma (OSCC) before treatment. A total of 113 patients (82 men, 31 women; median age, 64 years) with untreated OSCC were examined. Correlations between spontaneous pain in the primary site and sex, age, primary site, TN stage, clinical stage, and clinical growth type of cancer (exophytic or endophytic), as well as the degree of histological differentiation and the histological mode of invasion were evaluated. At the initial examination, 42 (37%) of patients had spontaneous pain. In univariate statistical analyses, reported pain correlated significantly with patient age and the clinical growth type of the cancer, as well as with the degree of histological differentiation and the histological mode of invasion. Multiple logistic regression analysis showed significant correlations between reported spontaneous pain and the clinical growth type of the cancer (P = 0.0003; odds ratio, 9.5; 95% confidence interval, 2.8-32.3), as well as reported spontaneous pain and the histological mode of invasion (P = 0.0026; odds ratio, 4.7; 95% confidence interval, 1.7-12.7). Clinical and histological endophytic growth patterns of OSCC might be significant risk factors for the presence of spontaneous pain before treatment.