The patterns of differential gene expression were examined in two primary (A's) and two matched-metastatic (B's) head and neck squamous cell carcinoma (HNSCC) cell lines by differential display of mRNAs and northern blot hybridisation. Three cell lines used (PCI-04A, PCI-04B and PCI-06A) were established independently prior to therapy, whereas one cell line (PCI-06B) was established from a recurrent tumor after radiation therapy. A total of seven differentially displayed mRNA clones were identified, of which six clones were obtained by comparison of PCI-06A cells with PCI-06B cells (SCC-S1a/b, SCC-1c, and SCC-S2, PCI-06B; SCC-S3 to SCC-S5, PCI-06A), and one clone was obtained from the PCI-04A and PCI-04B match (SCC-Sa, PCI-04B). Based on the DNA database search for homology to the known sequences, six of the seven partial cDNA clones (SCC-S1a/b, SCC-1c, SCC-S2 to SCC-S4, and SCC-Sa may represent novel genes, whereas one cDNA clone (SCC-S5) shows significant homology to the HLA class II antigen gene (DPW2 beta chain). Each of the seven clones revealed preferential expression by northern blotting in the cell line of origin as compared to the matched counterpart. The transcripts ranged in size from approximately 7.0 Kb to 0.5 Kb. Interestingly, the SCC-Sa clone was preferentially expressed in both metastatic cell lines compared to the primary tumour-derived cell lines. We conclude that the SCC-Sa gene may be more commonly involved in tumour metastasis, whereas expression of the other genes (SCC-S1a/b, SCC-S1c, SCC-S2-SCC-S5) may be associated with metastasis and/or response of HNSCC to ionising radiation.