Two patients presented with takotsubo cardiomyopathy after chemotherapy. Neither of the patients had any known cardiac history until the initiation of chemotherapy. These patients were treated with different chemotherapy regimens appropriate to their malignancies. After chemotherapy initiation, they presented with symptoms ranging from exertional dyspnea to cardiogenic shock requiring intra-aortic balloon pump and pressor support. Cardiac catheterization demonstrated characteristic apical ballooning with nonobstructive coronary artery disease. Both of the patients demonstrated a transient reduction in left ventricular function which resolved on follow-up echocardiography. These cases suggest a potential novel etiology for takotsubo cardiomyopathy.