Calcium ion plays vital roles in virtually all aspects of cell physiology and biology. Dysregulation of calcium homeostasis emerges as an important hallmark for tumor cells. Remodeling in the expression, activities, and localizations of calcium channels and transporters is common to tumor progression. Elevated intracellular calcium prompts uncontrolled growth during tumor formation, whereas lowered calcium appears to be anti-apoptotic in the later phase of tumor progression. Moreover, local and global calcium oscillations may facilitate and guide cell migration in metastasis. These recent advances suggest that targeting calcium signaling may afford potential therapeutic strategies to intervene the tumor formation and progression.