The observations that mammary neoplasms of mice transgenic for H-Ras, Myc, Neu, Notch4 and SV40-Tag, and that papillary carcinomas of BALB/cJ mice are exclusively composed of cells with a luminal phenotype, are consistent with the hypothesis that these neoplasms arise from a cell committed to the luminal lineage. Here, NOTCH4 is linked to thyroid gland papillary carcinoma.