Fourteen specimens of normal, benign, or malignant tumor cells from the head and neck region were subjected for culture using 0.2% of irradiated collagen gel embedding technique. Re-differentiation of glands within the gel in serum-free medium was observed. There were marked differences in the growth patterns within the gel between normal or benign and malignant cells. Four normal glands and 5 out of 6 benign tumors showed branch-like growth patterns. On the other hand, malignant tumors showed no branch-like pattern, or could not grow at all. The results showed that the collagen gel technique could be useful for the differential diagnosis of malignancy in head and neck tumors.