Background/Objectives: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease for which serum vascular endothelial growth factor D (VEGF-D) is a recommended diagnostic biomarker. Data from the Russian Federation remain limited. We aimed to evaluate the diagnostic accuracy of VEGF-D in women with multiple pulmonary cysts and to assess diagnostic thresholds in a Russian cohort. Methods: In a single-center prospective cohort study, 71 women aged 20–74 years with multiple lung cysts on high-resolution computed tomography were enrolled. Serum VEGF-D levels were measured using Quantikine ELISA. Diagnoses were established according to international guidelines. Receiver operating characteristic analysis was used to evaluate diagnostic performance and identify cut-off values. Results: Of 71 patients, 48 (68%) had definite LAM. VEGF-D levels were higher in LAM than in non-LAM patients (1425 ± 872.1 pg/mL vs. 552 ± 276.5 pg/mL, p < 0.0001). The area under the curve was 0.866 (95% CI 0.783–0.950). A cohort-derived threshold of 738 pg/mL yielded 81% sensitivity and 79% specificity. VEGF-D levels of 800 pg/mL or higher were observed in 75% of LAM cases. Conclusions: Serum VEGF-D demonstrates high diagnostic value for LAM in women with multiple pulmonary cysts in the Russian Federation. The findings support implementation of VEGF-D testing in routine practice and are consistent with use of the internationally recommended 800 pg/mL threshold for noninvasive confirmation in most patients.