Malignant cells appear to possess a special aptitude for survival. We attempted to prove this in vitro by acute nutritional and energy deprivation as a survival threat. A phosphate-buffered saline (PBS) survival test in cell culture allowed static observations. These were supplemented by classic and quantitative phase-contrast time-lapse microscopy. From one normal and four neoplastic cell populations, no cells survived 77 hours of exposure to PBS. Only G3S2 derived from a human breast carcinoma survived 60 hours. Cells in sparse culture were more vulnerable than those in dense. Epithelial cells were more vigorous than mesenchymal cells. Cells of greater malignancy resisted longer. Evaluation in culture as detailed by digital holographic microscopy (DHM) revealed an increase in the compactness of the intracellular mass motility from normal to metastasizing mesenchymal cells, thus reaching the level of epithelial G3S2 cells. Studying the PBS survival test with DHM opens a new approach to investigations of the structural integrity of neoplastic cells.