Coccidioidomycosis is associated with an increased risk of mortality and morbidity among immunosuppressed patients. The sensitivity of current commercial Coccidioides serologic tests is not well evaluated in patients with hematological malignancy. We conducted a retrospective study, including patients with culture-proven coccidioidomycosis, from October 1, 2017, to December 12, 2023. Cases with hematological malignancy and hematopoietic stem cell transplant (HM) were matched with an immunocompetent cohort (1:2) to compare the sensitivity of serology (enzyme immunoassay IgG/IgM or complement fixation) tests-matched by age, gender, and race. We matched 43 HM patients with 86 controls. The median age of the HM/hematopoietic stem cell transplant cohort was 67 (Interquartile Range [IQR], 52-75), 65% male, and 86% White. Most HM had lymphoma (37%), followed by leukemia (35%). Most cases had pulmonary infection (74%) versus controls (84%), P-value = .2, and 12% had a prior history of coccidioidomycosis compared to controls (17%), P-value = .4. Positive Coccidioides serology test results among HM were statistically significantly lower than controls (37% versus 72%), P-value ≤ .001. Multivariate conditional logistic regression identified HM and a history of coccidioidomycosis as statistically significantly associated with positive serologic testing, with Odds Ratio (OR) 0.27 (95% Confidence Interval [CI] 0.12-0.62, P-value = .002) and OR 6.07 (95% CI 1.25-29.4, P-value = .025), respectively.Coccidioides serology tests in HM patients with culture-proven coccidioidomycosis had low sensitivity. Given the increased risk of complications in this group, future studies are needed to evaluate more sensitive diagnostic tests.