We examined topographic distribution of p53 mutations using in situ PCR in three primary non-small cell lung cancers, showing distinct patterns of variable p53 overexpression by immunohistochemistry (Ebina, et al:Cancer Res. 54:2496, 1994). All tumor cell nuclei, regardless of the status of p53 overexpression, demonstrated homogeneous distribution of mutant p53 with specific primers, suggesting only subgroups of the mutated cells overexpressed p53 protein. Topographic genomapping using in situ PCR is a useful method to reveal the possible correlation between cell-morphology and molecular abnormality in cancer cells.