To improve the field of molecular medicine, traditional biochemistry has employed various approaches such as: electrophoresis; Western, Northern, and Southern—blotting techniques for protein, RNA and DNA respectively [
98]; enzyme-linked immunosorbent assay (ELISA) [
99]; gene silencing and RNA interference [
100]; gene cloning [
101]; conventional and real-time qualitative polymerase chain reaction (PCR) [
102]; karyotyping & fluorescence in situ hybridization (FISH) [
103]; Comparative genomic hybridization (CGH) [
104]; and chromosomal/cytogenetic analysis [
105]. However, many of these techniques are limited because they are low to medium throughput in their capabilities. These techniques have benefitted the field of oral pathology by enabling the identification of molecular markers of various diseases. For example, cytogenetic alterations such as copy number gain of 16q, 8q and loss 3p, 8p, 9p, 4q, 5q, 13q have been found to be biomarkers for premalignant oral lesions; while copy number gain of 3q, 8q, 9q, 20q, 7p, 11q13, 5p and copy number loss of 3p, 9q, 21q, 5q, 13q, 18q, 8p have been found to characterize oral squamous cell carcinoma [
106‐
109]. Molecular alterations such as microsatellite instability (MSI), abnormal mismatch repair protein (MMR) proteins MLH1, PMS2, MSH2, MSH6, and loss of heterozygosity (LOH) of 9p21, 3p14 have been found to characterize premalignant oral lesions [
106‐
108,
110,
111]; while perturbation of
p53, EGFR/STAT, COX-
2, NF-
κB, VEGF, TGF-
β/Ras pathways have been found in oral squamous cell carcinoma [
112‐
114]. Identified potential biomarkers of metastatic oral squamous cell carcinoma includes E-cadherin, integrins, matrix metalloproteinases (
MMPs), IL-8, chemokine receptor 7 and
EGFR [
111]. Various fusion oncogenes have been used as potential biomarkers of salivary gland tumours; such as
MYB-
NF1B t(6:9)(q22-23:p23-24) for Adenoid cystic carcinoma [
115];
CRTC1-
MAML2 t(11:19)(q21-22:p13) for low or intermediate grade Mucoepidermoid carcinoma [
116];
ETV6-
NTRK3 for Mammary analogue secretory Carcinoma [
116,
117];
PLAG &
HMGA2 for Pleomorphic adenoma [
118,
119];
EWSR1-
POU5F1 t(6:22)(p21:q12) for high grade Mucopeidermoid carcinoma [
116];
EWSR1-
ATF1 t(12:22)(q15:q12) for low grade hyalinizing clear cell carcinoma [
120];
NUT-
BRD4 t(15:19)(q14:p13.1) for NUT midline carcinoma [
121,
122]; and
MECT1-
MAML2 for low grade Mucoepidermoid carcinoma [
123]. Considering the impact of tradition molecular biology advances on diagnosis of tumors in the head and neck region, it is plausible that emerging high throughput omics based techniques would even bring greater breakthroughs to diagnostic oral pathology practice.