It is often easy to distinguish between primary brain tumors and metastases based on morphology alone. However, in some cases immunohistochemistry (IHC) is necessary to obtain a diagnosis, but, as the present case report illustrates, this is not always straightforward. A 75-year old man was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed no enhancement in the lung, so the tumor was treated as a GBM. Eight months after the primary diagnosis a new MRI revealed metastases in the spinal cord, but there was still no enhancement in the lungs. We reviewed the literature concerning markers used to differentiate between GBM and SCLC and found that most of these markers showed limited specificity. It is further discussed whether the case illustrates an example of spontaneous regression of primary SCLC or might be an example of a GMB metastasizing to the spinal cord. Although immunohistochemical markers are of great help in many situations, the case illustrates important limitations and the need for better diagnostic markers.