BACKGROUND: The management of hypersensitivity to excipients and food additives remains a significant issue for healthcare professionals and patients. Avoiding carboxymethylcellulose (CMC) can be a considerable challenge for patients allergic to CMC due to its widespread use. We assessed the tolerance of CMC through different route of administration in a patient with a confirmed CMC allergy. We conducted a literature review to analyze all relevant cases of patients allergic to CMC, focusing on tolerance through non-injectable routes. METHODS: Skin tests, basophil activation tests, oral and nasal provocation tests with CMC were performed to evaluate patient's hypersensitivity. RESULTS: Skin tests and basophil activation tests with CMC were positive and confirmed IgE-mediated hypersensitivity to CMC in the patient. While the patient tolerated oral administration of CMC and CMC-containing eye drops, nasal provocation test resulted in asthma exacerbation and rhinitis. CONCLUSION: Tolerance of CMC appears to be route-dependent. Provocation tests with CMC through various routes of administration are essential for assessing tolerance and providing appropriate recommendations for patients with CMC allergy.