Depressed and flat surface lesions are not easy to identify with routine colonoscopies during screening for colorectal cancer (CRC). Identifying clinically relevant genes that influence tumor shape could be useful when screening for the presence of depressed lesions. Total RNA was extracted from tumor cells collected by laser microdissection from the primary lesions of 146 CRC cases. Microarray analysis was performed to identify genes that were differentially expressed between depressed and elevated tumors. Single nucleotide polymorphism (SNP) analysis of genomic DNA from the peripheral blood of 67 CRC patients was then used to associate polymorphisms with the occurrence of depressed tumors. Microarray analysis revealed significantly higher expression of the fibronectin 1 (FN1) gene in 129 depressed-type tumors and lesions compared to 17 elevated-type tumors. FN1-abundant CRC tumors were large with a significantly higher incidence of lymphatic permeation. SNP analysis indicated that 44 tumors with a GG genotype at SNP rs6707530 showed significantly higher FN1 expression than did 23 tumors with GT/TT genotypes (p<0.05). The product of the FN1 gene (located at 2q34) is involved in cell adhesion, migration and metastasis in mesenchymal tumors. Abundant expression of FN1 may allow cancer cells to invade deeper layers, which would eventually define tumor shape. Identification of this SNP in blood samples may facilitate disease diagnosis and allow prediction of the presence of depressed tumors in the colorectal epithelium before a colon fiberscope examination.