Hiccups generally are self-limiting and of short duration. Those lasting more than 48 h or recurring at frequent intervals are termed persistent. There are numerous causes of hiccups, with medications implicated only rarely. While hiccups are usually benign, severe attacks may lead to exhaustion, eating difficulties, and affect quality of life. We report a case of severe hiccups in a patient receiving chemotherapy (oxaliplatin, 5-fluorouracil, leucovorin) for metastatic colorectal cancer. Hiccups began on the day following chemotherapy and continued constantly for over 30 h until relief was obtained by sucking the juice of a fresh lemonade. A similar pattern occurred in the next two chemotherapy cycles. Dexamethasone had been prescribed as prophylaxis against emesis and this was considered a possible cause. Withholding dexamethasone in the next cycle led to elimination of hiccups without having an impact on control of nausea and vomiting. A number of case reports have linked corticosteroids, particularly dexamethasone, to the occurrence of hiccups. Antineoplastic agents have occasionally been reported as causing hiccups; however, in most of these cases, corticosteroids, as part of the treatment protocol or as antiemetics, may have been a more likely cause. This case serves an as important reminder that adverse effects appearing during chemotherapy may not necessarily be due to antineoplastic agents. In the case of hiccups, oncology health professionals should review all medications and non drug-related factors before assigning causality.