Background: Managing thrombosis in rare sites is challenging. Existing studies and guidelines provide detailed explanations on how to overcome lower-limb thromboses and pulmonary embolisms, but few studies have examined thrombosis in rare sites. Lack of data makes clinical practice heterogeneous. Recommendations for diagnosing, treating, and following-up internal jugular vein thrombosis are not clearly defined and mostly based on adapted guidelines for lower-limb thrombosis. Case presentation: A 52-year-old Caucasian woman came to the Emergency Department with chest, neck, and left arm pain. Computed tomography imagery showed a left internal jugular vein thrombosis. An extensive workup revealed a heterozygous factor V Leiden gene. Therapy was initiated with intravenous unfractionated heparin, then switched to oral acenocoumarol, which resolved the symptoms. Based on this case presentation and a literature review, we summarize the causes, treatment options, and prognosis of unprovoked internal jugular vein thrombosis. Conclusions: Managing internal jugular vein thrombosis lacks scientific data from large randomized clinical trials, partly because such thromboses are rare. Our literature review suggested that clinical treatments for internal jugular vein thrombosis often followed recommendations for treating lower-limb thrombosis. Future specific studies are required to guide clinicians on the modalities of diagnosis, screening for thrombophilia or oncologic disease, treatment duration, and follow-up.