Laryngeal cancer is a significant disease worldwide, which presents an increasing incidence. Two contrasting ideas of the immune system role during cancer development are accepted: (1) it fights tumor cells, and (2) it aids tumor progression. Thus, there is no clear understanding about the immune response in laryngeal cancer. Furthermore, since tobacco is the main cause of laryngeal cancer and it contains various carcinogenic components, including metallic elements, these may play a role on cancer development. Plasmas of patients with laryngeal cancer and of healthy smokers were evaluated by 2D gel electrophoresis and mass spectrometry. Proteins were detected on every gel around pH 4.0-10.0 from molecular mass of 10-60 kDa. Few differences were found among cancer and control patients. However, three spots gathered between pI 7.3 and 7.6 with different molecular masses appeared exclusively in cancer profiles. From ten spots identified, six correspond to immune system components, including the three differential ones. The latter were observed only in cancer patients. The presence of several trace elements in the identified proteins was determined by inductively coupled plasma mass spectrometry, where chromium was increased in all proteins analyzed from patients with cancer. This study reinforces the importance of the immune response as target in the understanding and treatment of laryngeal cancer and the possibility that chromium is important in the carcinogenic progress.