Dear Editor, It has been demonstrated, that DNA from the Merkel cell polyoma virus (MCV) is monoclonally integrated in the genome of Merkel cell carcinoma (MCC) cells in the majority of tumors. 1 In this respect, Bathia et al. recently reported an observation in THE JOURNAL which suggests that two subgroups of MCC can be distinguished on the basis of the abundance of MCV; moreover, these subgroups differed in their expression of cancer related proteins, ie the Retinoblastoma protein (RB). 2 The authors report that MCV DNA load was less then one copy per 300 cells in 14 of 23 MCC tumors (60%), and that these tumors were characterized also by loss of RB expression. In the remaining samples, which were characterized by high levels of RB expression, the estimated viral load was always higher than 1 copy per 20 cells. Noteworthy, only in two cases viral load was higher than 1 copy per 2 cells. In consequence, the authors speculate on a possible mechanism in MCC with a minority of infected cells contributing to transformation of uninfected neighbouring cells by paracrine mechanisms. 2 However, the results of Bathia and colleagues are in contrast to another recently published paper describing the viral load in MCV þ MCCs to be generally> 1 copy per tumor cell as measured by quantitative PCR. 3 Moreover, immunohistological analyses of MCV þ MCCs demonstrated that nearly every tumor cell expressed the MCV large T-antigen (LTA) protein. Confirming this latter report, our own immunohistochemical analysis of MCC tissues confirms this pattern of LTA expression, ie virtually every tumor cell of MCV þ MCCs is expressing LTA protein (Fig. 1a). Moreover, we analyzed genomic DNA purified from 50 MCC tissue samples for the presence of MCV by Real time PCR. Relative quantification of the samples was calculated by the DDCt method normalized to the repetitive DNA elements LINE1; genomic DNA of a MCC cell line that harbours at least two concatemerized copies of the MCV genome in every cell served as calibrator which allowed to approximate the minimal copy number per cell in the tissues. To this end, MCV DNA was undetectable in only 7 of the 50 samples (14%). In those samples with detectable MCV DNA the median of the estimated minimal copy numbers is approximately 1 copy per cell (Fig. 1b). Indeed, 63% of the MCV positive cases (27 samples) demonstrate minimal copy numbers higher than 0.5 copies/cell. Even some of the values below 0.5 may still be in accordance with 1 MCV copy per