A profile of transcript abundances from multiple genes constitutes a molecular signature if the expression pattern is unique to one cell type. Here we measure mRNA copy numbers per cell by normalizing per million copies of 18S rRNA and identify 6 genes (TIE1, KDR, CDH5, TIE2, EFNA1 and MYO5C) out of 79 genes tested as excellent molecular signature markers for endothelial cells (ECs) in vitro. The selected genes are uniformly expressed in ECs of 4 different origins but weakly or not expressed in 4 non-EC cell lines. A multi-gene transcriptional profile of these 6 genes clearly distinguishes ECs from non-ECs in vitro. We conclude that (i) a profile of mRNA copy numbers per cell from a well-chosen multi-gene panel can act as a sensitive and accurate cell type signature marker, and (ii) the method described here can be applied to in vivo cell fingerprinting and molecular diagnosis.