Systemic therapy for malignancy may be accompanied by an acute coronary syndrome (ACS), regardless of cardiovascular risk factors. We present three patients with few cardiovascular risk factors and no history of cardiovascular disease, who suffered an ACS within a week of starting systemic treatment of colorectal cancer, non-Hodgkin's lymphoma and breast cancer, respectively. In all three patients, systemic anti-cancer therapy was continued after making individualised adjustments to the treatment regimen. It is important to recognize the possible relationship between chemotherapy - including the oral compound capecitabine - and ACS, and to withhold systemic anti-cancer treatment until the ACS is adequately treated. Subsequently, a decision has to be made regarding the continuation of the systemic anti-cancer treatment. Factors to be included in decision making are the intent of the treatment (curative or palliative), the availability of a regimen with less cardiovascular toxicity but comparable efficacy, the outcome of the ACS and the patient's wishes.