The extracellular portion of AXL can be cleaved off from the Masitinib membrane to generate soluble AXL, which is present in conditioned media from cancer cells as well as in human sera. In a recent publication, the levels of sAXL were reduced in patients with renal cancer compared to normal controls. In contrast high levels of sAXL correlated to worsen prognosis within the same patient group. Herein, we set out to investigate the feasibility using soluble AXL as a marker to assess NF1 related tumor burden. The MPNST and neurofibroma cells differ from the normal Schwann cells in the expression of receptor tyrosine kinases, making them excellent candidates for drug interventions. So far most of the studies have focused on a few selected RTKs such as EGFR and PDGFR, but the clinical trials using drugs that target these receptors have had limited effects. Here we utilized a phospho-RTK array measuring the activity of 42 different RTKs. In addition to EGFR and PDGFR that has previously been reported in the context of NF1, we found increased phosphorylation of AXL in the MPNST cell lines. The AXL receptor tyrosine kinase was up-regulated in benign and malignant nerve sheath tumors compared to normal Schwann cells. The soluble form of AXL was found in conditioned media of MPNST cells and in the plasma from mice harboring human MPNST xenograft tumors. Moreover, the level of human sAXL in mice correlated to the size of the tumors, while there was no human sAXL detected in uninjected mice. We verified these data in a second xenograft model, in which mice were treated with photodynamic therapy using an increasing concentration of Lipo-Chlorine Ce6. As expected, the level of sAXL correlated to the tumor size in all three treatment groups, further emphasizing the role of sAXL as a biomarker for tumor burden. Finally, the level of sAXL was elevated in NF1 patients with plexiform tumors compared to patients with only dermal neurofibromas and controls. With a trend towards a high level of sAXL in patients with high number of dermal neurofibromas compared to that of the patients with fewer tumors. The expression difference of AXL between benign and malignant tumors is still unclear. One of the patients in the study had his leg amputated in order to remove the Plexiform/MPNST tumor. He donated the leg to our study and we obtained Plexiform/MPNST tumor, benign neurofibromas and normal sciatic nerve tissues from his leg. In this patient we found strong expression of AXL in the excised nodular neurofibroma, while the plexiform/MPNST tumor from the same patient had lower levels; however, it was still higher than that of the normal sciatic nerve. Histological examination of the Plexiform/MPNST tumor, showed a malignant transformation in some parts, and it is unclear whether the part that was analyzed in this experiment had malignant or benign cells. The other two MPNST samples in this study had high levels of AXL, as did 1 out 4 dermal neurofibromas. The other three dermal neurofibromas had intermediate levels between the sciatic nerve and the malignant tumors.