There have been numerous publications linking Ca²⁺ signaling and cancer, however, a clear explanation for this link has remained elusive. We recently identified the oncogenes/tumor suppressors Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) as regulators of the expression of STIM1, an essential regulator of Ca²⁺ entry in non-excitable cells. The current review focuses on the literature defining both differential Ca²⁺ signaling and WT1/EGR1 expression patterns in 5 specific cancer subtypes: Acute Myeloid Leukemia, Wilms Tumor, breast cancer, ovarian cancer, glioblastoma and prostate cancer. For each tumor-type, we have assessed how specific changes in WT1 and EGR1 expression might contribute to aberrant Ca²⁺ homeostasis as well as the therapeutic potential of these observations.