Early diagnosis is the key to achieve better patient survival in cancer. Targeted molecular imaging and therapy are considered as the best approaches for early detection and better management of cancer. But the paucity of reliable biomarkers that express in the earliest stages of cancer present a major challenge to develop high sensitive imaging probes and effective therapies. Recently, we applied a unique unbiased two-color combinatorial cell surface screen and identified cell surface vimentin (CSV) protein as an earliest cancer biomarker, while identifying a peptoid called JM3A as a specific ligand to target Vimentin. Our approach here was unique, because we transformed primary HBEC3 bronchial epithelial cells into full malignancy by introduction of sequential genetic alterations of p53, KRAS and cMYC and finally compared those transformed cells (e.g. HBEC3p53, KRAS, cMYC) to the normal HBEC3-KT cells in an unbiased fashion to identify newly appearing biomarkers on the transformed cell surface. Here we hypothesized that any new biomarker that appeared responding to those basic oncogenes on these transformed cells should be the earliest possible biomarkers for malignancy. We have performed preliminary studies to confirm Vimentin is present on HBEC3p53, KRAS, cMYC cell surface and absent on normal HBEC3-KT cell surface. We also validated JM3A indeed as a Vimentin binding peptoid, its specificity towards early cancer cells, and performed IHC studies in human early cancer tissue immunohistochemical (IHC) studies and multiple other diagnostic tests. We also performed medicinal chemistry improvements on JM3A and conducted multiple biological assays (e.g. MTS, clonogenecity) to find the therapeutic utility of our peptoid. JM3A can be utilize as a low cost alternative for antibodies in research applications as well.