In our previous studies, we used global computational differential display of ESTs that belong to UNIGENE clusters and identified human sequences differentially expressed in human tumors, as well as a considerable amount of transcripts represented only in tumor-derived cDNA libraries. Most of the tumor-specific EST clusters are derived from the plurality of the tumor types originated in tissues of both ectodermal and mesodermal origin. We found that many of such tumor-specific ESTs do not contain long open reading frames and cannot be classified as protein-encoding genes. To experimentally assess patterns of expression of these EST clusters, we studied four of them in PCR experiments on Clontech MTC panels. The experimental data confirm the results obtained by in silico screening, i.e. tumor specificity of their expression. We suggest that a significant increase in the expression of non-coding RNA is a fundamental feature of cancer cells, and that such transcripts could serve as markers for the diagnosis or monitoring of human malignancies.