Purpose: Introduction: Seronegative celiac disease in selective IgA deficient patients is a known phenomenon. Presented is a case of seronegative celiac disease in a patient with hyper-IgM syndrome. Case Presentation: A 23-yearold Caucasian male presented with a three day history of nausea, vomiting, and abdominal pain. Past medical history was notable for hyper-IgM syndrome secondary to CD40 ligand deficiency, chronic pancreatitis, and autoimmune hemolytic anemia requiring splenectomy and chronic immunosuppression. A four year history of chronic diarrhea, abdominal cramping, and inability to gain weight was also reported. An EGD performed in 2007 was grossly normal, yet duodenal biopsies displayed mucosal flattening with chronic inflammation. Serologies performed at that time showed: IgA tTG=0U/mL, IgG tTG=0U/mL, IgG AGA=1U, and IgA EMA=0. The diagnosis of celiac disease was discounted. On admission, the patient appeared malnourished and under-developed, with a normal skin exam. Laboratory workup showed: albumin=3.4g/dL, AST=187U/L, ALT=83U/L, alkaline phosphatase=599U/L, direct bilirubin=0.2mg/dL, and lipase=382U/L. BMP, CBC, and lipid panel were unremarkable. An EGD revealed scalloped mucosa in the 2nd and 3rd parts of the duodenum with lack of villi under water magnification. Duodenal biopsies demonstrated marked villous blunting, crypt hyperplasia, and dense lymphocytic infiltration of the lamina propria (Fig). The patient was started on a gluten-free diet and symptoms improved. Discussion: Hyper-IgM syndrome is a rare disease in which patients present with normal to elevated IgM levels and low levels of IgG, IgA, and IgE. Seronegative celiac disease in selective IgA deficiency is well described. Despite having elevated IgM levels, our patient was deficient in all other immunoglobulins, including IgA. Regardless of having a complicated medical history, his clinical symptoms corresponded with the diagnosis of celiac disease. To our knowledge, no other seronegative case of biopsy-proven celiac disease has been reported in a patient with hyper-IgM syndrome. Conclusions: Celiac disease can be overlooked if relied on serological markers alone. Small intestinal biopsies should be performed in cases where there is a strong clinical suspicion, even if serology results are negative.Figure