Sequestration of Plasmodium falciparum-infected erythrocytes is crucial to parasite survival as it prevents destruction in the liver and spleen. Knobs have been considered necessary but not sufficient for cytoadherence to vascular endothelial cells in vivo and to melanoma or umbilical vein endothelial cells in vitro. We describe here a knobless clone that cytoadheres strongly to C32 melanoma cells. This clone cannot express the knob-associated histidine-rich protein (KAHRP) due to the deletion of the KAHRP gene. Our results raise the possibility of an alternative mechanism for in vitro cytoadherence and suggest that the use of long term cultured isolates and melanoma cells as a model for cytoadherence in vivo may be misleading.