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Nephrotic syndrome (NS) has a well-established relationship with hypercoagulability and, while rare, is known to present with unprovoked venous thromboembolism (VTE). Here, we present a case of seemingly unprovoked deep vein thrombosis and pulmonary embolism as presenting features of NS. We explore the challenge of timing diagnostic renal biopsy with necessary therapeutic anticoagulation, particularly in patients who present with unstable or extensive VTE. We also examine relevant factors in selecting an anticoagulant and discuss emerging treatment modalities in NS. This case underscores the complexity of medical decision-making in NS presenting with VTE and highlights the importance of multi-disciplinary consideration of patient-specific risks and benefits., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thummala et al.)