Nanoparticle uptake and cell death following addition of magnetite nanoparticles (MNPs) with a diameter of ∼10 nm were evaluated in three histological types of human mesothelioma cells, NCI-H28 (epithelioid), NCI-H2052 (sarcomatoid), and MSTO-211H (biphasic) cells, and human breast cancer MCF-7 cells. Dose-dependent cell death was observed in MSTO-211H cells but not in MCF-7 cells, although cellular uptake of MNPs was observed in both cell types. Mesothelioma NCI-H28 and NCI-H2052 cells showed behavior more similar to that of breast cancer MCF-7 cells than that of mesothelioma MSTO-211H cells. DNA fragmentation and microarray analyses suggested that MNPs induced transforming growth factor β2 related apoptosis in MSTO-211H cells. On the other hand, the viability of human mesothelioma cells containing MNPs with a diameter of ∼40 nm was investigated after exposure to an alternating magnetic field. Temperature increase under the alternating magnetic field and high rates of cell death were observed in all three histological types of human mesothelioma.