Background/Aim: Invasive lobular carcinoma (ILC) of the breast has a low complete-response rate in the neoadjuvant-chemotherapy setting. The addiction to methionine is a fundamental and ubiquitous characteristic of cancer cells, termed the Hoffman effect. We have previously targeted methionine addiction of breast cancer with recombinant methioninase (rMETase) using patient-derived orthotopic xenograft (PDOX) models. The aim of the present study was to determine the efficacy of methionine restriction with rMETase and a low-methionine diet combined with first-line neo-adjuvant chemotherapy, in a patient with metastatic ILC of the breast. Case Report: A 62-year-old female was diagnosed with metastatic ipsilateral axillary-lymph-node recurrence of breast ILC 3 years after mastectomy. The patient underwent [ 11 C]methionine positron-emission tomography (METPET) which showed extensive methionine accumulation in the ipsilateral axillary lymph nodes, indicating the presence of cancer cells. The patient received standard neo-adjuvant chemotherapy, which consisted of 3 months of doxorubicin and cyclophosphamide followed by 3 months of docetaxel from March 2022. The patient also went on a low-methionine diet and daily oral rMETase as a supplement every 6 hours concurrently with six months chemotherapy. The patient's blood carcinoembryonic antigen (CEA) level decreased gradually, and computed tomography findings showed loss of axillary lymph-node metastases in the first 3 months of neo-adjuvant chemotherapy with doxorubicin and cyclophosphamide combined with rMETase and a lowmethionine diet. Α complete response was demonstrated by METPET at 6 months, at conclusion of docetaxel chemotherapy. Conclusion: Combination therapy of doxorubicin and cyclophosphamide followed by docetaxel combined with methionine restriction led to a remarkable complete response that is expected in fewer than 10% of patients with ILC of the breast treated with neo-adjuvant chemotherapy alone. The present results suggest that methionine restriction in combination with doxorubicin and cyclophosphamide followed by docetaxel may be effective, after METPET has demonstrated the presence of methionine-addicted axillary-lymph-node metastases in ILC of the breast.Breast cancer is the most common cancer type and the second cause of death in females in the United States (1). Invasive breast cancer is a histologically heterogeneous disease with many histopathological subgroups. Invasive lobular carcinoma (ILC) is the second-most prevalent type of invasive breast cancer following invasive ductal carcinoma (IDC), accounting for 5% to 15% of all breast cancer cases (2). ILC is more likely to be hormone-positive, human epidermal-growthfactor-receptor-2 negative, and have a lower proliferative index compared to IDC. ILC has a lower complete response rate to neo-adjuvant chemotherapy but better recurrence-free and overall survival than IDC (2-4).