We have previously reported on the expression of interleukin-4 receptor (IL-4R) on many solid cancer cell lines. In the present study, we have examined the expression of IL-4R on head and neck cancers in situ by immunohistochemistry. Seven primary squamous cell carcinomas of the head and neck region were stained by a monoclonal antibody to human IL-4Rp140 protein (M-57). We report that all squamous cell carcinoma samples were positively stained although at variable intensity with anti-IL-4R antibody. Tumors stained with IgG control did not show any staining. On the other hand, six benign lesions from the same anatomical area showed faint or no staining at all. Three uterine endometrium samples were also negative for the IL-4R expression. In contrast to published contrary results, we did not observe any effect of IL-4 on the proliferation of four squamous cell carcinoma of head and neck (SCCHN) cell lines examined. These results demonstrate that human squamous carcinoma of the head and neck express IL-4R, which could be targeted for diagnosis and therapy by anti-IL-4 receptor antibody fused to toxins or radionuclides or alternatively by IL-4 toxins.