In humans, mirtazapine can prevent chemotherapy-induced nausea and vomiting (CINV) and improve cancer patients’ quality of life (QoL). This drug is being increasingly used as an appetite stimulant in cats. The hypothesis of this retrospective study was that mirtazapine could reduce the incidence of CINV and weight loss in feline patients affected by lymphoma. The objectives were to report the use of mirtazapine transdermal ointment and assess the incidence of gastrointestinal (GI) toxicity and weight loss in cats diagnosed with lymphoma and receiving chemotherapy. Transdermal mirtazapine was topically administered to the inner surface of the pinna (2 mg/cat/daily) for 14 days following chemotherapy administration. Data recorded from 20 patients were collected. Different grades of GI toxicity were shown in 8/20 (40%) patients. Body weight (BW), body condition score (BCS), and muscle condition score (MCS) improved in 12/20 (60%), 6/20 (30%), and 2/20 (10%) cats, respectively. Mirtazapine-induced adverse events (AEs) occurred in 4/20 (20%) cats and did not require mirtazapine discontinuation. Substantial weight loss was not encountered, suggesting that patients had an adequate food intake after chemotherapy administration. Transdermal mirtazapine ointment was considered safe and well tolerated.