We report a case of delayed methotrexate (MTX) clearance following administration of a complementary medicine containing chlorophyll. A 54 year-old male with relapsed primary cerebral lymphoma and normal renal function (CrCl 126mL/min) was treated with methotrexate 3g/m2 intravenously monthly. Throughout treatment the patient self-administered a complementary medicine (Jason Winter’s chlorophyll®) which he was advised to cease during methotrexate treatment due to unknown potential interactions. For the first 4 cycles (pre-MTX CrCl 112–143mL/min), chlorophyll was ceased 2 days prior to commencement of methotrexate and withheld until methotrexate clearance. These cycles were administered without complication, with the methotrexate level reduced to ≤0.05umol/L within 3 days. Prior to cycle 5 (pre-MTX CrCl 110mL/min), the patient did not cease chlorophyll but there were no other changes to concomitant medications. A literature search found no specific interactions between methotrexate and chlorophyll. The chemotherapy was administered without delay or evidence of change in renal function but the methotrexate level 3 days post-administration was 1.20umol/L and did not reduce to ≤0.05umol/L until day 10. Consequently, from cycle 6-12, (pre-MTX CrCl 87–97mL/min) the methotrexate dose was halved, and the patient ceased chlorophyll 48 hours prior to methotrexate administration and until clearance. There were no further episodes of delayed methotrexate clearance. A sample of Jason Winter’s chlorophyll® was analysed for impurities, specifically salicylates, which could have caused impaired methotrexate clearance. A high performance liquid chromatography (HPLC) assay was developed to separate and quantitate the stated ingredients in addition to acetylsalicylic acid and salicylic acid, and any other unknown impurities. No impurities were detected. It is therefore likely the patient’s delayed methotrexate clearance was due to an interaction with chlorophyll. The case we have described is a novel association between the ingestion of chlorophyll and delayed methotrexate clearance.