In cetuximab-sensitive tumours, we identified several mutations in PI3K/AKT and RTK/RAS pathway genes, which would be expected to confer cetuximab resistance, including variants in BRAF, KRAS, PIK3CA, AKT1, FGFR1, and ERBB2. Our findings suggest that the presence of these specific variants alone is not sufficient to preclude an objective response to cetuximab. The gene discussed is PIK3CA; the disease is neoplasm.