In 2021, our group published a laboratory study on the impact of PBM on human gingival fibroblasts. The in vitro results confirmed the fact that the appropriately selected wavelength and properly selected parameters of the laser settings can increase cell proliferation, modulate inflammatory markers, and decrease the susceptibility of human gingival fibroblasts to apoptosis. Therefore, this case report was aimed at the clinical evaluation of the proposed settings and treatment regimen in a very difficult situation of an immunocompromised patient with extensive changes and stagnation of symptoms for many weeks. A 65-year-old man, during his oncological treatment, was diagnosed with oral mucositis grade 3 according to the World Health Organization and National Cancer Institute scales. Due to pain sensation, long-lasting and not healing oral lesions, and problems with solid food intake, he was qualified for laser photobiomodulation therapy. For the management of oral lesions, a diode laser 635 nm (SmartPro, Lasotronix, Poland) was intraorally applied at an energy density of 4 J/cm, the 20 s of irradiation, the output power of 100 mW, and in continuous wave mode. Seven treatment procedures were performed two times a week using the spot technique in contact and non-contact mode. Within 21 days of monotherapy, all ailments disappeared. The patient was also able to reuse dental dentures and return to a solid diet. The obtained results confirm the efficiency of at least 3 PBM protocols. Our case shows that the use of PMB therapy contributes to faster healing of painful oral lesions in oncological patients, and thus the treatment time and return to the appropriate quality of life is shorter.