<p>Merkel cell carcinoma (MCC) is an aggressive type of neuro-endocrine skin cancer and can be subdivided into Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. The nuclear lamina, consisting of A- and B-type lamins, is altered in different types of cancer and can be disrupted by viral infections. This study investigated A- and B-type lamin expression levels in MCPyV-negative and MCPyV-positive MCC cell lines in relation to the MCPyV status, using (live cell) imaging, qPCR, and Western blotting. MCPyV-positive MCC (non-adherent) cells showed lower A-type lamin and higher B-type lamin expression at both protein and mRNA levels as compared to MCPyV-negative (adherent) cells. Nuclear envelope (NE) ruptures were reversible in MCPyV-negative cells, while in MCPyV-positive cells these lead to cell death. Transfection of MCPyV-negative cells with small (sT) or large tumor (LT) antigens did not result in the expected decrease of A-type lamin expression. Future research into the correlation between A-type lamin expression levels and the different growth patterns, the occurrence of NE ruptures, the (lack of) NE repair in MCC cell lines, and the relation of lamin expression and tumor metastasis, will contribute to a better understanding of the molecular background of the aggressive phenotype of MCC.</p>